title: Treatment of Glucocorticoids Inhibited Early Immune Responses and Impaired Cardiac Repair in Adult Zebrafish.
abstract: Myocardial injury, such as myocardial infarction (MI), can lead to drastic heart damage. Zebrafish have the extraordinary ability to regenerate their heart after a severe injury. Upon ventricle resection, fibrin clots seal the wound and serve as a matrix for recruiting myeloid-derived phagocytes. Accumulated neutrophils and macrophages not only reduce the risk of infection but also secrete cytokines and growth factors to promote tissue repair. However, the underlying cellular and molecular mechanisms for how immune responses are regulated during the early stages of cardiac repair are still unclear. We investigated the role and programming of early immune responses during zebrafish heart regeneration. We found that zebrafish treated with an anti-inflammatory glucocorticoid had significantly reduced heart regenerative capacities, consistent with findings in other higher vertebrates. Moreover, inhibiting the inflammatory response led to excessive collagen deposition. A microarray approach was used to assess the differential expression profiles between zebrafish hearts with normal or impaired healing. Combining cytokine profiling and immune-staining, our data revealed that impaired heart regeneration could be due to reduced phagocyte recruitment, leading to diminished angiogenesis and cell proliferation post-cardiac injury. Despite their robust regenerative ability, our study revealed that glucocorticoid treatment could effectively hinder cardiac repair in adult zebrafish by interfering with the inflammatory response. Our findings may help to clarify the initiation of cardiac repair, which could be used to develop a therapeutic intervention that may enhance cardiac repair in humans to compensate for the loss of cardiomyocytes after an MI.
authors.affiliation: Department of Medical Science & Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Wei-Chang
authors.initials: WC
authors.lastname: Huang
authors.forename: Chung-Chi
authors.initials: CC
authors.lastname: Yang
authors.forename: I-Hui
authors.initials: IH
authors.lastname: Chen
authors.forename: Yu-Min Lawrence
authors.initials: YM
authors.lastname: Liu
authors.forename: Shing-Jyh
authors.initials: SJ
authors.lastname: Chang
authors.forename: Yung-Jen
authors.initials: YJ
authors.lastname: Chuang
mesh_terms: D000818:Animals; D005938:Glucocorticoids / Q000494:pharmacology*; D006352:Heart Ventricles / Q000276:immunology*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000276:immunology; D012038:Regeneration / Q000187:drug effects / Q000276:immunology; D015027:Zebrafish / Q000276:immunology*
chemical_list: D005938:Glucocorticoids